An in vitro bioassay developed in this laboratory will be applied to study tumor colonyformation by cells from primary explants of human tumors. Such clonogenic tumor cells are considered to be functionally related to tumor stem cells in vivo. The assay has proven applicable to supporting growth from a variety of human tumors and been applied to studies of human tumor biology and drug sensitivity. The current research proposal has several goals relevant to understanding biological modulation of in vitro tumour colony growth (e.g., by interferon-like activity), as well as to examine tumor heterogeneity and differentiation, and to assess drug sensitivity and resistance in human cancer. Clinical correlations will be sought in prospective trials of standard and new agents to define the relevance of clonogenic assays to cancer chemotherapy and new drug development.